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tv   Charlie Rose  WHUT  July 20, 2012 11:00pm-12:00am EDT

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>> rose: welcome to our program, tonight a special edition of the charlie rose brain series year two. in our 10th episode we consider a amyotrophic lateral sclerosis and spinal muscular atrophy. >> we're going to have today amyotrophic lateral sclerosis and spinal muscular atrophy, two diseases that affect motor neurons. and this is a continuation of a theme we've had for the last several programs. we will consider disorders that affect the motor system. now if you are going to affect any cell type, and really have an impact it's hard to think of one that is more critical for our behavior than the motor neuron. this is the output element of the nervous system. this is responsible for all of our actions. >> rose: episode 10 of the
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charlie rose brain series 2 underwritten by the siemens foundation, coming up. >> the charlryios brain series is about the most exciting scientific journally of our time. understanding the brain. the series is made possible by a grant from the siemens foundation. their mission is to advance the fron tears of research in the basic sciences and mathematics. funding for charlie rose was provided by the following:
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. >> from our captioning sponsored by rose communications from our studios in new york city, this is charlie rose. >> rose: tonight we continue our exploration of the magnificent brain with a look at amyotrophic lateral sclerosis more commonly known as als and spinal muscular atrophy or sma. both of these are defined by the loss of spinal motor
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neurons. sma generally strikes at birth or very early in life whereas als usually occurs at middle age or later. sma is an inherited disease and results in mutations in a beginning el single gene. currently there is no cure for either als or sma. lou gehrig the great baseball player who died from als once said, quote, i might have been given a bad break but i've got an awful lot to live for. two of my guests this evening might say the same, peter frates is the former captain of the boston college baseball team. after he college he moved to hamburg where he played in the german baseball league and coached kids in the sport. he was diagnosed with als earlier this year. griffen kingkiner is entering the 8th grade and participates in a table tennis, arch ree, swimming and field events. he was diagnosed with sma five years ago. griffen's mother beth kingkiner joins us, a
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elementee schoolteacher. finally two positions at the forefront of research, neil shneider of columbia university and richard finkle. an once again my cohost is dr. eric kandel, noble lawyer yet, professor at columbia university and a howard hughes medical investigatorment i'm pleased to have all of them and as always we begin with eric kandel and a sense of what we hope to accomplish this evening. welcome. >> we're going to consider today amyotrophic lateral sclerosis and spinal muscular atrophy, two diseases that affect motor neuron os. and this is a tjs of the theme we've had for the last several programs. which are considered disors that affect the motor system. we began by considering park inson's disease and hunts ton's disease, two diseases that affect motor systems that are due to protein folding disorders. then we considered multiple sclerosis, which has a very
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different mechanism. it is an autoimmune disease in which the immune system attacks the mylin sheath. these two sets of disorders have different mechanisms of action but they share in common the fact that they're fairly widespread in their clinical manifestations. this is in contrast to the two diseases we're going to consider today. als and spinal muscular atrophy which are specific to motor neurons. this is interesting from several points of view. to begin with it shows you that a single nerve cell in the brain is so complex that you can disturb different pathways and produce quite different disorders in the same cell type. now if you are going to affect any cell type it
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really have an impact it's hard to think of one that is more critical for our behavior than the motor neuron, this is the outfuture element of the nervous system this is responsible for all of our actions. and when you think about the fact that everything we do for ourselves and communicating with other people involves movement, our aspirations, our goals, our fantasies, our perceptions all ultimately leads to action. you realize that this is really one of the defining elements of our behavior. as sharington without won the nobel prize in 1932 for his studies of motor neurons said in a wonderful quote, to move things is all that mankind can do. for such the sole exec eter is the muscle whether whiz pell-- whispering a syllable or selling the forest. what causes all of these movements is muscle and the muscles are controlled by motor neurons there are two types of motor neurons.
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upper motor neurons and lower motor neurons. the lower motor neurons are located in the spinal cords and they control our limbs, our legs, our arms, our chest, our breathing. muscles are our face. the upper motor neurons are located in the cerebral cortex and motor cortex and regulates the motor cells. we are first going to consider amyotrophic lateral sclerosis which was discovered by the great friend neurologist. and this is a disorder that commonly begins with either lower upper motor neurons but after a while it usually involves both of them. the incidents of als is between one and two people per 100,000. and it's onset as you indicated is in later life. it has two forms. it has a genetic form which
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is a minority form, about 10%. and the common form is sporadic. so a number of different causes which we really don't understand. we know very little about the sporadic form. but with the genetic form, the inheritable form, we now know a number of genes that contribute to this. and this is always an important handle in trying to understand the disease because these genes give you clues, these mutations as to what goes wrong in the disease. and that hopefully will give you some idea as how you might be able to try to treat the disease. in spinal muscular atrophy this is a very different disorder. this is a disorder that begins in childhood, that is completely hereditary. all forms of it are inherited. the gene that is involved, the mutation sits in chromosome 5 and in the codes of protein that is essential for the survival of motor neurons.
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in fact, one can know about the severity of the disease if one has some idea of the level of the protein that is present in people that have the disorder. it's if they lose most of the protein the disease is quite severe. if they retain much of the protein the disease is milder. now although amyotrophic lateral sclerosis is calle called-- disease in many countries throughout the world, we in the united states and specifically we in new york like to think of it as lou gehrig's disease and i like it particularly because lou ger significant a graduate of columbia and this is my community. now lou gehrig developed als at the peak of his career. he had been an outstanding hitter for many seasons, .330, .-- .350 batting average. and he first noticed the disorder when he noticed
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that his swing was not as sharp as it used to be. a terrific hitter. he noticed all of a sudden that while he was seeing the ball perfectly well he wasn't getting his bat around fast enough to really meet it effectively. and i think it's wonderful that we have griffen and peter here because these are the lou gehrigs of our round table. >> rose: they're athletes. >> they're fantastic athletes. they're extremely skilled. griffen is an outstanding athlete in many categories. now an outstanding javelin thrower, and he first noticed his difficulty which is sma in the course of seeing and an interference with his athletic performance. and his mother beth is with us. and she can actually describe the early evidence that he had this disease. with peter who is a phenomenal baseball player, comparable in many ways to lou gehrig, he also noticed it in his athletic
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performance. and to sort of complete the circle, we have with us richard finkle who is going to tell us about sma which is his specialty. and he's been taking care of griffen so he knows a great deal about him. and we have neil schnyder who say specialist in als and will give us insight, not only into the care of patients with als but also both of them are physician scientists, interested in trying to understand the mechanism of the disease in order to get therapeutic intervention for it. so we're going to learn a lot about motor neuron disease not only from people who have it but from people who study it. >> rose: let me begin with you. have you enlarge on what dr. kandel just said and give us a sense of what it's about. >> well, amyotrophic lateral sclerosis, als, as we heard is a motor neuron disease. it's named in this country
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for the yankees hall of famer lou gehrig who first brought this disease to america's attention. in france it's called charcoze disease named after the pathologist without first described it in the 19th century and in britan and elsewhere it is referred to simply as motor neuron disease. als is a neurodegenerative disease like alzheimer, like huntington and parkinson's disease that you have spoken about on this program before. and it's similar in the sense that it involves the degeneration of a particular population of neurons in the central nervous system. in the case of als the degenerating neurons are motor neurons that reside in the motor cortex in the brain stem and in the spinal cord. at the end stage of disease in als the vast majority of motor neurons are lost. and this is shown in this first image. this is a section through the spinal cord, on the right from the patient with als and on the left from a similarly aged patient without died of other causes.
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and what you see are these large darkly stained neuronhe i, those are motor neurons in the spinal cord. and on the right you can see i think it's clear that motor neurons are almost completely gone. normally the upper motor neuron in the motor cortex activates the lower motor neuron in the brain stem and spinal cord. what you see depicted is that the lower motor neuron sends, relays that signal from the upper motor neuron to the muscle, producing a muscle contraction and moving a joint. that's how we make a movement. but as motor neurons degenerate the motor axe ons retract and this connection is lost. and the muscles that are involved become wasted a trophic, and weak. the muscles that are involved include the muscles of the limb that move our arms and legs and control our posture, include the bulbar muscles that control talking, chewing, swallowing and include the respiratory
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muscles. the diaphragm and accessory muscles of breathing. patients with ald progressively lose their ability to lose their hands. they lose their ability to stand, then to walk. they lose the ability to talk and to wall swallow and als is ultimately fatal because patients lose the ability to breathe. at the moment there is no cure for als. and i think it's fair to say no treatment that significantly changes the natural course of the disease. but in recent years we've really made tremendous progress in the care of als patients through a multidisciplinary approach involving clinicians from a variety of specialties that help als patients and their families manage the progressive symptoms and to maximize the length and i think more importantly the quality of their lives for as long as they live with this disease. >> rose: peter, thank you for coming, first of all. the hallmark of this series of programs is to have people who are living with the disease come and tell us their own perspective on it. >> sure.
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>> rose: so we would love to hear you talk about your life and how you come to know about this. and how you deal with it. >> exactly. as dr. kandel described earlier, this is a disease that attacks the motor neurons that i'm dealing with now. but obviously since diagnosis earlier this year on march 13th, i have learned a great deal about this disease and that actually i am kind of an outlier of an outlier disease. whereas usually it affects mostly males 55 to 75, and at age 27 i was 10 years younger than when lou gehrig himself was diagnosed. so life before diagnosis was very normal. athlete, three sport athlete, in high school, went on to play boston boston college where i captained the team in '07. as we'll see in a video here, i was 6 foot 2, 225 pounds, you know, cut out of granite and ready to roll.
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so --. >> rose: cut out of granite. >> that's what somebody told me once. but so i was able to-- . >> rose: put some wood on the ball. >> as will you see here, that's what i, what i wanted to do with my life was play sports and continue on. so -- >> swing the bat today with a lot of confidence. >> only had one hit in the three game series last week. against north carolina for boston. >> he could really do some damage here with jarrod mcguire at third base, jeff ruiz is at second. and joseph ayers who just walked is down at first base. and that is hit high and
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deep, going back,-- watches it, out of here, that's a grand slam home run for peter frates. second home run of the year. wow! >> you know, i was ready to role that senior year, ready to play professional baseball which i did over in europe in germany for a year. so that was great. and i continue to play baseball for the last five years in the summer, around the boston area where i live. one of the first symptoms i noticed was my bat speed wasn't as quick to the ball. still playing the outfield fine, throwing the ball fine but that quick reaction from the pitch to the plate, i just said you know, the year before i won mvp of the league, batted .400. and this year i'm sitting around .250 and really having some struggles at the plate. so eric mentioned wanted to
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us kind of compare and contrast my averages with lou gehrig toward the end of his career and i think it actually paints a very nice picture of what this disease can do. as you see with the blue line there being lou gehrig's batting age and the red being mine it's very similar. >> i think yours is slightly better, no. >> we had a little bit easier competition, i think. but it paints a nice picture of, you know, and it made me question what is going on here. something is amiss. and at the end of that season i was struck with a pitch during the championship series in my left wrist and this is what lead me down the path of finding out what was wrong there was nerve damage so we eventually saw a neurologist. the neurologist asked me about what other symptoms we were having. and i said well, you know, i'm kind of tired a lot. i have stumbled and i'm not really unbuttoning my shirt and tying my tie as easily
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as i was for work. so we came in for a second visit, did a full body test and the diagnosis was made maybe a month afterwards, after doing some expensive testing. and being an athlete i know my body very well. and once i started realizing some things were going wrong, i went on the web site, stumbled upon als symptoms. there were about a dozen there. and i maybe had 10 out of 12 hit very much home for me. so i accepted it. and realized that i had to make some strides here and get the word out. and i just appreciate you having me here to be able to help do that. >> rose: how are you living with the disease? >> well, you know, if you look at me sitting here, you wouldn't notice that i have a degenerative motor neuron disease. i may slur my words a little bit or but other than that i look like every day normal guy. but during the day, you know, getting changed is one of the earlier things that
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folks have trouble with. buttoning this is my outfit i wear to work every day. there is no way i could put this together by myself now. tying shoes, walking has become significantly slowed down. walking up and downstairs is very challenging. and these are all early symptoms. so there are more to come. but as dr. neil mentioned earlier we are very hopeful that some treatments are on the way and we'll be able to, extend the quality of life and in the end find a cure for and reversal for this disease. >> rose: dr. shneider compare his story with the stories, especially his youth. >> pete's story is typical in a lot of ways. and the incidents as eric said of als in the population is one or two in 100,000 per year. that means that one in every 500 people born will die of
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als. and just to give you a sense of how that compares. the annual incidents of als is similar to multiple sclerosis which you talked about in your last program. but the prevalence of als, that is the number of people living with asl at any one time is much less. and that's because als progresses so rapidly and patients die so quickly, relative to ms. on average our patients live about two to three years after onset of symptoms. about 20% of our patients live for five years. and about 10% live more than ten years. as we've heard a couple of times als is an adult onset disease. most people who get it are in midlife in their 40s and 50s. the yaeferj average onset is about 55 years of age. people are completely normal in advance of the onset of the disease as pete was. but the range of ages that
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we see is also quite wide. we see a juvenile form of the disease. i've seen children in their mid and late teens with typical als. and i see people late in life in their 80s and 90s who first present with the symptoms who had a perfectly normal, healthy and active life beforehand with no signs to suggest that this was their future. als is clinically defined as a selective motor neuron disease that affects both the upper and lower motor neuron as eric has told us. when the upper motor neuron degenerates patients experience certain signs that include weakness of muscles but also spasticity, increase in tone, a stiffness of the mussle that affects gait and balance and speech amongst other things. when the lower motor neuron in the brain stem and final cord are affect wed first see twitching of the muscles, something maybe that you experience. >> one of the first signs was twitching. >> and after twitching
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sometimes people experience painful cramping, and that's followed, of course then by wasting and weakness of the affected muscles. either the upper motor neuron signs or lower motor neuron signs can predominant in any given patients but we typically see a certain pattern of disease. another striking aspect of als as eric mentioned is its predominance to the motor system. so just to give an example, even late in the course of the disease when patients are severely weak, even paralyzed, the sense soar system is still entirely normal. patients can still feel touch, temperature, vibration all normally. we don't understand the basis of the selectivity but very interesting question for people who study the disease. but that's not to say that als is exclusively motor neuron disease, since we know that patients experience nonmotor symptoms. so for example patients often will describe these unusual bouts of laughing or
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crying that are offen socially inappropriate and a little bit embarrassing and don't reflect how they're actually feel teg moment. clearly not a motor system but something commonly described by patients with als. but in all cases, symptoms progress steadily in patients with als, fast never some than others for reasons we don't really understand. and what is often i think so difficult for patients is that they are continually being asked to accommodate to new challenges, new disabilities, new inabilities in the course of their disease. our response as clinicians is sort of reactive that is when a patient has difficulty walking we first offer a cane and then a walker and then ultimately a wheelchair. when swallowing is too compromised so they can't take enough food by mouth and gets enough calories we place a feeding tube directly into the stomach. when breathing is compromised and a patient is uncomfortable we use noninvasive means, similar
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to what people use for sleep apnea to force, physically force more air into the lungs. and this works for a time, for a limited period of time. but at some point all patient its have to face the very difficult decision of whether or not to be placed on a respirationer, on a breathing machine for the rest of their lives. this is always a very painful decision for our patients and their families. it's a deeply personal decision that is informed by many factors including the stage of life a patient is finding themselves in, the cultural background, religious beliefs, financial means. all of these play a role. and our role as physicians is to introduce end of life issues earlly-- early enough in the course 6 of a person's disease to give them time to consider how they want to live with the disease and ultimately how they want to die with it. and so that decision of whether or not to be on a
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respirator is not made in an emergency and not by somebody other than the patient him or herself. >> rose: okay. are you also obviously a new friend of mine, a patient of yours and a very good friend of mine and appeared on this program a number of times. in his role as a public intellectual and a historian, especially of europe. i had an opportunity because of my great respect for him to do a conversation with him after he was living with als. and here are some excerpts from that inter view. >> rose: tell me about how you found out and how you adjust to the idea of this illness. >> well, it's one of the-- that i have lou gehrig's disease but -- -- the keys on the
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keyboard, then progressivel progressively-- walking up hills, -- >> bugs driver-- there's nothing you can do.
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do you do nothing. because i'm a writer, then a teacher, i was able to continue for two years after diagnosis. >> rose: the reason we watched that video and the reason we're here to talk about this, to understand and for more people to understand about this disease. the reason pet certificate here and the reason that everybody comes to this table is so that there is a greater and broader appreciation all in the hope, all in the hope that somehow through all of this, through the research of people, through a recognition that we will find ourselves much faster becoming a clearer approach to some kind of cure and treatment it is never easy but i think people who live with disease more than anybody else are desperate to know more, to learn everything as peter suggested. he went on his own search at google. so one more time i want to
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thank all of you for being here for that purpose. peter, you see this. you know thing pro fr fro-- prognosisment you live with hope that something can be done am but just give me a sense of how you look at the future. >> sure. and you know my outlook on the future right now is very unclear. i had some, as we all do, plans of grandeur, of having a family, the white picket fence, having a great job, things 6 that nature. right now that's not certainly for me. lou gehrig was diagnosed in 1937. now 2012. and frankly, we haven't made much progress since then. i actually watched lou's final speech the other day, watched it a few times and i watched his every little nuance. how he walked, how he walked, how he was handed a plaque and he directed it directly towards the ground because he wasn't strong enough to hold it upment these are all exact symptoms and thing i go through on a daily basis
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in 2012. so you know, i look at the arena, als arena right now and i know there's some great momentum but at the same time, i realize my prognosis is, very similar to tony's or very similar to a lot of als patients i see on a day-to-day basis. when you're in a wheelchair with a respirator people may think this person is completely out of it. they have no idea what's going on. they have totally checked out but as neil mentioned, we can hear, smell, breathe, feel just the same as anyone else. it's almost just imagine being trapped inside your own body because your brain function is as sharp as a tack. so i have, i realize that this is a possibility and i am, that's what drives me every day to get up in the morning and create awareness and let people know that this is not your grandfather's disease, this is a serious problem that i think needs to be rectified. we are passing away so
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quickly that there is not enough people to make enough stink to say listen, this needs to be changed. but with the help of folks like dr. neil, dr. kandel and the wonderful people that i'm treated with, we are, really making some great strides so that's why i join the board of directors for an organization called-- for life which was started in '06 by a gentleman named avi cramer from israel. he was diagnosed in '04, his first semester of harvard business school and him and his friends decided, those ivy leaguers being very smart like we are said we need to change. and we need to adapt on how we are raising funds and raising awareness. and price for life is exactly what it describes. it's incentive based research. you bring us a 3r06 entreatment for als we will write you a check for $1 million. and it's created a great buzz and there aren't just als people researching this. people from all over the world vying for that prize
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and we're hoping that you know this will expedite the process of finding some good treatments and that's why i'm optimistic and very hopeful for the future. >> rose: you actually don't think those ivy leaguers are any smarter than people that went to boston college. >> we hear they went to harvard because they couldn't get on the bc baseball team. >> eric, i'm right there with you. >> rose: richard, thank you for coming up from orlando. tell me about sma. >> sma is genetically based, 100% of the time. it's tallty-- actually fairly common. the most common fatal genetic disease in infancy and yet most people have never heard of it. that is because many of the babies don't live very long. and unfortunately, at the most severe end, it's really quite a striking disease. and similar to what we saw on the video with the who needed breathing support, nutritional support, that same level of intensity needs to be considered with these babies with sma.
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but one of the main distinctions even though it is a motor neuron disease just like als and it's a neurodegenerative disease where these motor neurons fail, and that's a cross-section of the spinal cord very similar to what neil showed us just before in als. and on the top you can cease those purple staining cells. those are the motor neurons that should be there. and in the bottom panel you can see that same section of the spinal cord from a baby with sma and the absence of those motor nears on. almost an identical picture to what we saw in als and yet the basic mechanism behind it and the cause and the way it evolves is really quite different as eric pointed out initially. so sma is called spinal muscular atrophy because it's these nerves in the spinal cord, that's the spinal part. an when those motor neurons fail it leads to muscle wasting or atrophy it was
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first described in the 19th century around the same time as als but the genetic basis wasn't identified until 1995 so about midway through my career hi already been seeing babies and children with sma for about 15 years and then the gene was identified and that changed everything. and i want to talk a little bit about that because that's really focused our understanding of the disease and some treatment strategies. but first i want to give you a sense of what the broad clinical range is. and we break sma down into four types. and we break it down into types one, two, three, four. and type one is the most severe form it presents in little babies in the first few months of life. and unfortunately they don't thrive very well. and without feeding support, breathing support, often they don't reach their first birthday. but now with better management we've learned to be able to keep these babies going and many actually get to age ten or so but at great expense. and the same ethical issues and technical challenges
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that we have with als we're facing with these little babies with sma. so that's the type 1 form of sma. and next is what we call type ii. and that's an intermediate form that presents later in infancy, somewhat less severe. these babies do get to sitting but they don't walk. the type 1 babies unfortunately they don't roll, they don't sit but the type ii children they get to sitting. and what's most interesting is there's typically a long platteau period. they will get to sitting. they never walk but they stay pretty of the same. and at age 20 they're not too different than they were at age 2. over that time course, however, they do develop increasing problems because it's a progressive disease. they're having problems with their breathing. they made need some breathing support. they have trouble with their feeding and they need nutritional support with feeding tubes and they get curvature of the spine and need orthopedic surgery to
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correct that. so these children are living longer. they're adults often livering into the 20s or 30s. but with limited function. next is called the type iii and that's where griffen comes in. i will let him talk about that in a minutement but the type iii children are perfectly normal early in childhood. you wouldn't pick them out as having any problems at all but over the course of the typically first few years of childhood they start to notice some weakness and there may be some tremor. and different from the little twitches what they call the fasiculation in arntion ls often we see a fine little trem never the hands and that may be the first coup clue in the sma particularly in the type iii child. fortunately type iii and the adult type 4 form which is pretty rare, we don't see the breathing problems. they will grow up to be healthy adults. they have normal life span. so one of the differences between als which is more of
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a linear decline and when we see sma there's this plateau period that is really quite striking. and it comes in these different flavors of severity. type 1, 2, 3, 4. another notable difference is it doesn't have the upper motor neuron issues like we have in als. so those are the main issues of sma. i wanted to just bring up a couple pictures and i'll show you now. and this is a little child, a little baby that i took care of some years ago and you can see how she's lying in bed, arms and legs sort of floppy to the side. her chest is collapsed. she is being fed through a little tube that goes down into her stomach. and unfortunately that baby didn't live very much longer after that picture was taken. and i want you to compare it now with the next photograph which is a child with type ii. and here's a cute little girl. who is sitting but you can see she's having to prop herself up. she's not quite sitting upright.
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she's needing to support herself. and this little girl never achieved walking. she's now several years older and is able to get around with the use of a little power wheelchair. she's smart as the dickens. and i think again it gets back to some of peter's comments that it is a cruel disease in some ways because these children are so smart it doesn't affect the brain. but it does zap their energy and motor function. >> rose: let me turn to griffen now. we're again pleased to have you here, griffen. >> thank you. >> rose: tell me about you and your life experience and coming to discover you had this disease. >> well, my life wasn't much different than anybody else. i was just as strong as everybody else growing up. but like at around 8 or so i was falling more and i wasn't as fast as everybody. and restarted noticing something was up so we went to the doctor and found out. but before that i was just a normal kid. >> rose: what did the doctor tell you. >> at first they didn't really know what it was. they were just trying to find out, running many tests. and like they were afraid of
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some things that it could bement when we found out t wasn't that bad. >> rose: and what are you doing now to adapt? >> i just-- . >> rose: how is your life different. >> i can't keep up with my friends sometimes if they try to run away. or maybe sometimes i'm tired and i can't do as many steps. but other than that i'm pretty strong and i can do good. >> are you still activeate let-- ate letically. >> uh-huh. >> what do you do the njdc which is wheelchair and ambulatory sports. i'm best at throwing the javelin and things like table tennis, arch ree, swimming and just field sports. >> rose: your mother is with you. last time you looked. share your experience with us as well. >> well as dr. finkle mentioned the first thing we really noticed was the tremors. when he was about 2 years ol before he had any other kind of symptoms he was a very active baby. he started walking at nine and a half months old, he was running around. but these tremors bothered
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us so we took him to a neurologist early on and they were always diagnosed as benign. they bothered us but we kind of just put it in the back of our minds. but when he got a little bit older and started playing every sport he could possibly play, baseball, flag football, soccer, golf, anything that he could get involved in he got involved in. we noticed that he was much slower than the other children. and then when he was playing travel baseball, we actually noticed that he was having trouble playing catcher, getting up from the ground with all of the equipment on so that bothered us. and we decided to investigate further so we went back to the neurologist who ultimately referred us to the mda clinic at children's hospital and that is where we met dr. finkle. and it took a little while because type iii sma is not nearly as common as the more severe types. so it wasn't obvious that that was what his issue was. and it took some time and some tests. and ultimately he was diagnosed with sma. and of course, we went home
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and we did all the research and tried to figure out what it was. we came to the conclusion that this looked like a disease that could be cured. and it actually wasn't as bad taxco have been. so we became very hopeful that there would be things for griffen so that he could continue to enjoy the sports that he loves so much. but in the meantime we did realize too that as he got a little bit older he wasn't able to continue the regular sports with the other children his age. and that's when we found really great team out of children's specialized hospital, lightning wheels so he participates with lightning wheels now and leaves for arizona tomorrow for national junior disability championship. >> rose: that's right, you're going to do well, aren't you. >> yeah. >> rose: give us the larger ethical picture here. >> that's a real concern particularly with the young babies. because i think each parent needs to struggle with do i have a feeding tube put in and have my little baby put on a breathing machine.
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which will extend life. but what about the quality of life. and what are we really doing. and obviously it's hard to really ask the baby are we doing the right thing so we have to be the surrogate and try to make the right decision. and it puts the physician in a difficult bind because it's not one size fits all. if the parent elects to go with the course of the feeding tube and the breathing support, but it's not the right thing for all parent its and i think we do have to introduce early on that there is a strong medical and ethical basis for what we would call palliative care. we do have to try to individualize it. but having said that, the statistics are really quite remarkable. if you looked back about 15 years ago, just talking about the type one babies with the most severe form, about 20 or 30% reached their second birthday. and lived longer. now it is more like 80%. and there have been many efforts i would say in its past 10 to 15 years with
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different advocacy groups. and they've made a huge effort in educating the public and in trying to get parents together, the muscular distrophy association covers both als and sma and many other neuromuscular disorders but they're targeted groups as well. there's the families of sma. there's sma foundation based here in new york and a consortium in europe, sma europe, all pretty much with the same idea of trying to provide individual educational sport to parents so they can make the right choices. it brings up a difficult challenge which is when is the treatment most likely to be effective. probably early on in the course before they have had this loss of the motor neurons because we don't yet know how to replace those. so the idea is if we have all these babies because half of sma are the little type 1 babies, are we going to have to start doing
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newborn screening to pick them up before they show signs of sma. that gets into a real thorny ethical dilemma and also a lot of technical challenges there. but that's really what the field is exploring at the moment. >> pick up on this conversation here about understanding the causes. >> . >> als is very different from sma in its causes. it is predominantly a spor atic disease that is, typically occurs in patients with no family history as is the case. >> correct. >> but in about 10% of cases of als it's familiarial that is it is inheritsed from one parent to another off then a dominant fashion. >> rose: so that is 890-10. >> yeah. the cause of sporadic als is essentially unknown. various triggers have been suggested and explored including environmental toxinsing trauma, inflammation, infiction and while all of these may play
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some role in either the onset or progression of motor neuron degeneration in als, none of them it seems has a primary role in the disease in contrast familiarial als the cause is known. it's always its again, a genetic problem. it due to a mutation in one of a really growing number of genes known to cause als and as you can see the list here, many of these genes have been discovered in just the past five years. and what has been an absolutely extraordinary period of research in als genetics. >> a real surge in the last five years. >> absolute surge. just to make the point the last gene on the list was just reported this week in the journal nature. so the genetics of this disease are very complex. and it presents a challenge to the field which is to understand how these seemingly unrelated genes and the proteins they encode how they are, in fact, related. how is it that a mutation in
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any one of these agains can cause selective motor neuron degeneration in als. you hit think of it as links in a chain where each of these als proteins plays a critical role in the pathway necessary to keep motor neuron as live so it's possible to break that chain at any point along os length and cause als. so the goal then is to identify these shared pathways and to target them for drug discovery. >> rose: if you can identify the genes, the most, the hope is that somehow there is a drug that can affect the gene behavior. >> yeah. the goal is to identify targets for drug discovery. and the question is what are those targets in als and to which forms of the disease do they apply. much of als research in the past decade really has focused on the familiarial forms of the disease which are i told you relatively rare. but one might ask the
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question why, why focus on this rare, on this rare form of familiar dwral als and not the vast majority of cases which are sporadic. and the answer i think is that we believe that sporadic als and familiarial als are related diseases. they're related through shared common pathways similar to the different forms of familiarial als. >> they are related in consequences as well. >> indeed. so we know for instance we know this for a long time that sporadic and familiarial als are clinically indistinguishable so when a patient comes in to see us they show the same con tell says of upper and motor neuron signs and symptoms that i described. and even very experienced als clinicians can't distinguish familiarial from for addic disease on clinical ground as loan. also path logically the two are very similar. >> rose: are you optimistic that yong the hordzon there
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are's answers to the questions we raised this evening. >> we're at a press i pits now with vi targeted-- precipice now with targeted treatment force sma that are coming on-line. and let me give a little background to perhaps explain where this is coming from. and you'll see that there is an elegant understanding of what is going on here. we know that every one of us should have something called an smn 1 gene that produces an important protein called smn protein. and that protein is critical to the function of these motor neurons. and in children with sma there's a change in the dna or mutation in that gene, it's absent. they're not making any of this critical protein. fortunately there's a second backup copy. and on the figure you can see that's on the right-hand side it's labeled smn 2. but it's not quite identical.
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and it has one little point that wobbles. and sometimes it makes a normal protein and sometimes it makes an abnormallal or nonfunctional protein. and it's that little bit of the functional protein that keeps these motor neurons going. and it's with that understanding which evolved in the late 1990s that many different treatment strategies have evolved. and to date we have had over 28 drug trials, different, eight different drugs that targn different ways this smn 2 gene. and the idea is how do we try to use that little wobl site. how do we try to direct it to make more of the normal protein that these motor neurons need and steer it away from producing a majority of this nonfunctional protein. so it's with that in mind that there was another very curious observation that came up. and we found out that in
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children with sma that you can have different copies, different number of copies of this smn 2 gene so the little baby that i showed with you the type 1 sma probably had two copies of that gene. and the little girl who is able to sit partly she probably had 3 copies. and we do know from griffen and he was kind enough to allow me to share his genetic information that he has four copies. so think of this as a multiplier effect. the more copies of it, the more protein you will make and the milder is the form of the disease process. >> it really gives you a completely new view of the disease. this shows you that that in addition to being a genetic disorder it is a deficiency disease like diabetes or hypothyroidism in which a critical product is in low supply. and it gives you hope that if you could find some way of increasing the supply of that, you could really improve and perhaps even reverse the disease it is an
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amazing new insight into the nature. >> it is a critical difference as well because neil was talking about the mechanisms in als where you are largely making an abnormallal sometimes toxic protein whereas in sma you make a normal protein, you just don't make enough of it. so there is enough to sort of keep that motor neuron going for a while and fortunately in a child with four copies like griffen he's doing pretty wellment but unfortunately the baby that might have one or two copies, it is just not enough to keep it going very longment but with that understanding of the genetic basis and the biology behind sma, several different treatments strategies have evolved. some of them are typical drugsing things that we could take as a pill or liquid and the idea is they get it from the bloodstream and they get into nerve cells and they try to trick that smn 2 gene into making more of the normal protein. unfortunately that strategy has not been effective so far. we've several different
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drugs have been tried and think just don't seem to have enough of effect that we can see any improvement in the children. but there are three new treatments coming on-line and one of them is very exciting. a little piece of dna. think of it as a molecular band-aid or patch and it attaches to this smn 2 gene and directs the pathway to create more of the normal protein. and clinical trials have just start in the its last few months in children with sma. we think that's very promising. coming on-line we hope in the next few years will also be gene therapy and stem cells so stay tuned. >> all right am i was in these programs by sching this one question. what question dow most want to see answered and i will start with you, griffen. >> how do we cure this disease. >> that's a very good one. >> the same. >> yours may be more scientific. >> well, it's getting back to that ethical dilemma of think we're going have good treatments. we need to know when it needs to be applied to have
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the max mall affect. and that's going to be tough to figure out. >> this is to din than alzheimer disease for every one feels by the time you see the symptoms you've had the disease for maybe a decade. so early diagnosis before symptoms are available is a common future of disease. you are just pushing it earlier into -- >> the biggest unmet needs is in the little babies with the type 1. if we can get it to work there obviously it will help griffen as well, the full spectrum. >> obviously i would like to know how we can find a cure but i think along with the disease a lot of motor neuron disease we have out there, what causes, how can we best get the word out, get the support we need because as neil mentioned the momentum is there. and if we get enough eyes and dollars on it i think we'll be on our way. >> find out what it causes and let's get to it. >> you got it. >> there's really been an explosion in als research. and all these ideas are now on the table. we have a lot of work ahead
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of us to sort through the different possibilities. i guess the one question i would want to know an answer to is how these different als genes are related. and is there a central fundamental pathway that is responsible for all forms of als and one that we might target. even to make a small difference in the lives of patients where now we have very little to offer them. the hope is very soon that we'll have something to make a significant difference in their lives. >> the more we know about sequencing genome and the more we are able to compare and compare data the more likely we'll come to some -- >> absolutely. >> yeah. my interest in this is its courage that griffen and peter show. the issues that they face, we all face. this end of life for everybody. and to see how they handle it and the courage they do this and how they maintain joy in their lives, knowing
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that you know, their life is compromised is amazing so from a psychological point of view to see the kind of character structure that people bring to bear on their disease i find absolutely fascinating. >> that is a lesson for all of us whether we're living with disease or not. so next episode where do we go. >> pain. pain is such a ubiquitous disorder. it's from, you know, getting hit with a baseball and feeling some transient pain to the terrible pachb cancer is, the pain of headache including migraine headache so there is a range of disorders that involves pain. >> thank you. again thank you each of you very much for coming here and sharing your conversation, your experience. thank you all.
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>> its charlie rose brain series is the most exciting scientific series of our time. understanding the brain. the series is made possible by a grant from the siemens foundation. their mission is to advance the frontiers of research in the basic sciences and mathematics. >> funding for charlie rose has been provided by the coca-cola company supporting this program since 2002. >> and american express. additional funding provided by these funders: and by bloomberg.
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